title: A patient-derived xenograft mouse model generated from primary cultured cells recapitulates patient tumors phenotypically and genetically.
abstract: BACKGROUND
  Preclinical trials of cancer therapeutics require both in vitro and in vivo evaluations. Recently, a patient-derived xenograft model in immunodeficient mice has been reported as a valuable in vivo evaluation system. In our current study, we aimed to establish a more efficient and accurate system for preclinical trials by generating primary cancer cells from patients and performing xenograft transfers of these cells into mice.
  
  
  METHODS
  Human lung cancer specimens (n = 4) obtained from chemo-naive patients were cultured in bronchiolar epithelial basal medium supplemented with growth factors, followed by inoculation into non-obese diabetic/severe combined immunodeficient mice. The generated tumors in the mice were validated phenotypically and genetically using the original specimen and primary cancer cells.
  
  
  RESULTS
  Immunohistochemical analysis of marker proteins, including cytokeratin 7, cytokeratin 20, epidermal growth factor receptor, thyroid transcription factor-1, CD56, chromogranin, and synaptophysin, demonstrated that the xenograft tumors were originated from the patient tumors. Moreover, mutation profiling using the OncoMap System, which analyzes mutations at 440 sites in 41 tumor-related genes, showed the same patterns in both the patient and xenograft tumors.
  
  
  CONCLUSIONS
  These results indicate that our animal system is suitable for the amplification of patient tumors and will therefore be beneficial for both in vivo and in vitro assessments and preclinical trials of chemotherapeutics. This has the potential to provide a very effective tool for future personalized therapy and for conducting translational lung cancer research.
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Seol
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Suh
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Ryu
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Chun
authors.forename: Deuk Chae
authors.initials: DC
authors.lastname: Na
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukamachi
authors.forename: Seong-Yun
authors.initials: SY
authors.lastname: Jeong
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Choi
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D061251:Primary Cell Culture; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor